RESUMEN
The anticardiolipin or antiphospholipid antibody syndrome is characterized by an increased incidence of venous and arterial thromboses. This syndrome may occur in association with systemic lupus erythematosus or independently. Gastroenterological manifestations have included Budd-Chiari syndrome, hepatic infarction, esophageal necrosis with perforation, intestinal ischemia and infarction, pancreatitis, and colonic ulceration. We report a 39-yr-old man with antiphospholipid antibody syndrome complicated by adrenal insufficiency secondary to bilateral adrenal infarction who presented with severe epigastric pain. Endoscopic evaluation disclosed progressive gastric ulceration with necrosis in the distal body. Angiography revealed no vasculitis. Because of intractable pain despite intravenous anticoagulation and narcotic analgesia, the patient was taken to surgery, and an antrectomy with Billroth II gastrojejunostomy was performed. Histological examination revealed widespread vascular occlusive disease involving veins, small arteries, and arterioles present in all layers of the stomach and the perigastric fat consistent with the vasculopathy of the antiphospholipid antibody syndrome. Treatment with high intensity oral anticoagulation and corticosteroids resulted in clinical and endoscopic improvement. This case report extends the gastroenterological manifestations of the antiphospholipid antibody syndrome to include giant gastric ulceration and emphasizes the importance of anticoagulation in treatment.
Asunto(s)
Síndrome Antifosfolípido/complicaciones , Úlcera Gástrica/etiología , Adulto , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/patología , Síndrome Antifosfolípido/cirugía , Gastrostomía , Humanos , Yeyunostomía , Masculino , Microcirculación , Estómago/irrigación sanguínea , Estómago/patología , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/patología , Úlcera Gástrica/cirugía , Trombosis/complicaciones , Trombosis/diagnóstico , Trombosis/patología , Trombosis/cirugíaRESUMEN
Mixed cryoglobulinemia is a systemic vasculitis with clinical manifestations ranging from the characteristic benign-appearing syndrome of palpable purpura, arthrologies, and fatigue to severe vasculitis involving vital organs. A strong association of the disease with hepatitis C virus infection and the demonstration of the specific concentration of the virus in the cryoglobulins have implicated hepatitis C virus in the etiopathogenesis of the disease. The increase in illicit intravenous drug use in the past 30 years seems to have raised the occurrence in the United States of this once uncommon disease and changed the demographics: there seem to be more male intravenous drug users in their forties with the disease than women without risk factors for hepatitis C virus infection in their fifties and sixties. Pathogenesis, therapy, and the hypothesis on the etiologic role of hepatitis C virus are reviewed, and the implications of recent studies and new concepts for treatment of this often benign-appearing but deceptive and potentially life-threatening disease are discussed.
Asunto(s)
Crioglobulinemia/etiología , Hepatitis C/complicaciones , Autoanticuerpos , Crioglobulinemia/tratamiento farmacológico , Crioglobulinemia/historia , Crioglobulinemia/inmunología , Femenino , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C/inmunología , Hepatitis C/virología , Historia del Siglo XX , Humanos , Masculino , Prevalencia , Factores de TiempoAsunto(s)
Antígenos CD/biosíntesis , Antígenos CD/genética , Antígenos de Diferenciación de Linfocitos T/biosíntesis , Antígenos de Diferenciación de Linfocitos T/genética , ADN Complementario/aislamiento & purificación , ARN Mensajero/biosíntesis , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , Ratones , Datos de Secuencia Molecular , Análisis de Secuencia de ADNRESUMEN
We present 10 cases of mixed cryoglobulinemia in patients infected with hepatitis C, including pertinent clinical, serologic, and pathological data. The findings attributable to MC appear to be similar in patients who are HCV-infected as in those with unknown HCV status. The prevalence of MC in HCV-infected patients appears to be lower in our region (13%) than in southern Europe (50-90%) although some of this difference is due to our requirement that patients included in our study have a cryocrit of at least 5%. In our patients, cryoglobulins were shown to be deposited in skin and kidney, but not in liver. The mechanisms by which HCV and MC are related remain uncertain. Although we and others have evidence for enrichment of HCV RNA in the cryoprecipitates of some patients, this was not always the case, and it is not yet clear that this finding is of fundamental pathogenic importance. Finally, it appears that some patients with HCV and MC may have a beneficial clinical response of vasculitic symptoms to therapy with alpha-interferon, as well as to glucocorticoids or other immunosuppressants. In our group, no predictors were apparent to distinguish responders from nonresponders before treatment. Similarly, the duration of response remains to be determined.
Asunto(s)
Crioglobulinemia/etiología , Hepatitis C/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Crioglobulinemia/tratamiento farmacológico , Crioglobulinemia/inmunología , Crioglobulinemia/patología , Femenino , Hepacivirus/aislamiento & purificación , Humanos , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ARN Viral/sangreRESUMEN
The CD6 glycoprotein is expressed primarily on lymphocytes and conveys co-activating signals to T cells, but its exact function and ligand(s) are unknown. A novel mAb, termed UMCD6, was demonstrated to recognize CD6 by immunoprecipitation, Western blotting, and reactivity with COS cells transfected with CD6 cDNA. UMCD6 was mitogenic for T cells and was strongly synergistic with phorbol ester in inducing T cell activation. UMCD6 enhanced the autologous mixed lymphocyte reaction as previously observed with another anti-CD6 mAb, anti-T12. The activating effects of UMCD6 were more striking than those of other anti-CD6 mAbs and encompassed all of the diverse stimulatory properties previously reported for other anti-CD6 reagents. However, neither UMCD6 nor other anti-CD6 antibodies alone or in combination with phorbol ester or IL-2 were able to induce thymocytes to proliferate. Stimulation by UMCD6 is dependent on accessory cell function in a manner not accounted for simply by antibody cross-linking. UMCD6 did not induce an increase in cytoplasmic free Ca2+, but the CD6 activation pathway appears to involve protein kinase C. UMCD6 and a panel of seven other anti-CD6 mAbs were used in a series of experiments to define four discrete epitopes of CD6 using the criteria of antibody cross-blocking, reactivity on reduced Western blots, and resistance to controlled V8 protease digestion. The functional mAbs UMCD6, 2H1, and anti-T12 each recognized a different epitope. Taken together, the results of these studies strongly reinforce the hypothesis that CD6 plays a significant and distinct role in T cell activation, and suggest that multiple regions of CD6 may be functionally active.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos T/inmunología , Epítopos , Glicoproteínas/inmunología , Activación de Linfocitos , Linfocitos T/inmunología , Células Presentadoras de Antígenos/fisiología , Calcio/metabolismo , Células Cultivadas , Humanos , Proteína Quinasa C/fisiologíaRESUMEN
A variant human H2B histone gene (GL105), previously shown to encode a 2300 nt replication independent mRNA, has been cloned. We demonstrate this gene expresses alternative mRNAs regulated differentially during the HeLa S3 cell cycle. The H2B-Gl105 gene encodes both a 500 nt cell cycle dependent mRNA and a 2300 nt constitutively expressed mRNA. The 3' end of the cell cycle regulated mRNA terminates immediately following the region of hyphenated dyad symmetry typical of most histone mRNAs, whereas the constitutively expressed mRNA has a 1798 nt non-translated trailer that contains the same region of hyphenated dyad symmetry but is polyadenylated. The cap site for the H2B-GL105 mRNAs is located 42 nt upstream of the protein coding region. The H2B-GL105 histone gene was localized to chromosome region 1q21-1q23 by chromosomal in situ hybridization and by analysis of rodent-human somatic cell hybrids using an H2B-GL105 specific probe. The H2B-GL105 gene is paired with a functional H2A histone gene and this H2A/H2B gene pair is separated by a bidirectionally transcribed intergenic promoter region containing consensus TATA and CCAAT boxes and an OTF-1 element. These results demonstrate that cell cycle regulated and constitutively expressed histone mRNAs can be encoded by the same gene, and indicate that alternative 3' end processing may be an important mechanism for regulation of histone mRNA. Such control further increases the versatility by which cells can modulate the synthesis of replication-dependent as well as variant histone proteins during the cell cycle and at the onset of differentiation.
Asunto(s)
Cromosomas Humanos Par 1 , Variación Genética , Histonas/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Southern Blotting , Ciclo Celular , Mapeo Cromosómico , Clonación Molecular , ADN/química , Células HeLa , Histonas/química , Humanos , Células Híbridas , Hibridación in Situ , Ratones , Datos de Secuencia Molecular , Precursores de Proteínas/genética , ARN Mensajero/genética , Endonucleasas Específicas del ADN y ARN con un Solo FilamentoRESUMEN
Leukocytes express a family of high m.w. glycoproteins called leukocyte common Ag (CD45), which are involved in phosphotyrosine signal transduction. Antibodies to different CD45 isoforms distinguish functionally different CD4+ T cell subsets in humans, rats, and mice. Selected protein isoforms are expressed through a process of exon splicing that is cell-type and differentiation-state specific. Splicing of the three variable exons, A, B, and C, which encode amino acids located near the extracellular amino terminus of the protein, potentially results in generation of eight different mRNA transcripts. The purpose of the present study was to determine the relative levels of all eight different CD45 transcripts present in a panel of murine CD4+ T cell lines and normal murine and human CD4+ T cell subsets separated with antibodies to CD45 variable exons. We show, as expected, that the broad features of CD45 surface isoform expression in these cells can be accounted for by the relative amounts of the eight differentially spliced transcripts. Unexpectedly, all the differences in CD45 isoform expression among the CD4+ T cell subpopulations that we measured could be accounted for by differences in the overall level of variable exon expression. We did not see differences among T cell populations in the relative expression of particular variable exons. Exon B was always found in greater abundance than exons C or A. Of the dual exon species, only AB and BC were found in CD4+ T cells. The AC species was undetectable. Human CD4+ T cells, especially those in the naive subset, express higher levels of CD45 variable exons than murine CD4+ T cells.
Asunto(s)
Antígenos CD/genética , Linfocitos T CD4-Positivos/fisiología , Antígenos de Histocompatibilidad/genética , Linfocitos T Colaboradores-Inductores/fisiología , Animales , Secuencia de Bases , Línea Celular , Exones , Expresión Génica , Humanos , Antígenos Comunes de Leucocito , Ganglios Linfáticos/fisiología , Activación de Linfocitos , Ratones , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos/química , Reacción en Cadena de la Polimerasa , Empalme del ARN , ARN Mensajero/genética , Bazo/fisiologíaAsunto(s)
Síndrome Antifosfolípido/inmunología , Autoanticuerpos/análisis , Enfermedades de las Válvulas Cardíacas/inmunología , Fosfolípidos/inmunología , Tromboembolia/inmunología , Enfermedades de las Válvulas Cardíacas/complicaciones , Humanos , Inhibidor de Coagulación del Lupus/análisis , Lupus Eritematoso Sistémico/inmunologíaRESUMEN
We analyzed the cell surface phenotype of CD8+ cells in both peripheral blood and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Utilizing the monoclonal antibodies anti-CD45RA, anti-CD29 and anti-S6F1-, one can define both suppressor effector (CD45RA+CD29-S6F1-) and killer effector (CD45RA-CD29+S6F1+) cells within the CD8 population. In patients with OA, normal proportions of CD8+CD45RA+, CD8+CD29+ and CD8+S6F1+ cells were found in both peripheral blood and SF. The peripheral blood of patients with RA, in contrast, showed a decreased percentage of CD8+CD45RA+ cells (13.4 +/- 2.6) (p less than 0.05), but a normal percentage of CD8+CD29+ and CD8+S6F1+ cells. In the SF of patients with RA, we observed a more dramatic decrease in CD8+CD45RA+ suppressor effector cells (6.4 +/- 5.0) (p less than 0.001), a significant increase in killer effector cells as measured by both CD8 + CD29+ (35.5 +/- 9.9) (p less than 0.001) and CD8 + S6F1+ cells (28.2 +/- 11.4) (p less than 0.01). These changes may contribute to the immunologic abnormalities previously noted in this disease and may provide some insight into the pathophysiologic mechanisms of RA.
Asunto(s)
Artritis Reumatoide/inmunología , Antígenos CD8/análisis , Subgrupos Linfocitarios/inmunología , Linfocitos T/inmunología , Adulto , Anciano , Antígenos CD/análisis , Artritis Reumatoide/genética , Femenino , Antígenos de Histocompatibilidad/análisis , Humanos , Integrina beta1 , Antígenos Comunes de Leucocito , Masculino , Persona de Mediana Edad , Fenotipo , Líquido Sinovial/inmunología , Linfocitos T Reguladores/inmunologíaRESUMEN
CD6 (T12) is a 130-kDa glycoprotein present on the surface of human T cells. Previously, we demonstrated that the anti-T12 and anti-2H1 monoclonal antibodies recognized different epitopes on CD6, and both were capable of transducing activation signals to T cells. Anti-T12 augmented suboptimal signaling via the TCR/CD3 complex and directly activated separated CD4+ but not CD8+ cells. Structural characterization of CD6 revealed that it contained intrachain disulfide bonds, was N-glycosylated, and in activated cells was phosphorylated on serine. Given the functional significance of CD6 and its involvement in signaling via CD3 and CD2 pathways, we examined in detail the biosynthesis, structural characteristics, and phosphorylation properties of this receptor-like molecule. These studies demonstrate that the nascent CD6 polypeptide on both T cells and thymocytes in 88 kDa, and the immature N-glycosylated form is 110 kDa. After maturation of N-linked glycan and addition of sulfated O-linked oligosaccharide, CD6 appears on the cell surface as a molecule of 130 kDa. CD6 is phosphorylated in resting cells and can be hyperphosphorylated when stimulated by phorbol 12-myristate 13-acetate, indicating that it may participate in the major common signaling pathway mediated through protein kinase C. Concanavalin A-activated cells are phosphorylated at an additional site(s) on the molecule and cannot be hyperphosphorylated with phorbol 12-myristate 13-acetate. These physical features reveal additional clues about the physiological role of CD6 and its mechanism of signal transduction and strongly suggest that CD6 represents a physiologically important membrane receptor involved in T cell activation.
Asunto(s)
Antígenos CD/biosíntesis , Antígenos de Diferenciación de Linfocitos T/biosíntesis , Glicoproteínas de Membrana/biosíntesis , Procesamiento Proteico-Postraduccional , Transducción de Señal , Linfocitos T/inmunología , Anticuerpos Monoclonales , Antígenos de Diferenciación de Linfocitos T/genética , Antígenos de Diferenciación de Linfocitos T/aislamiento & purificación , Humanos , Cinética , Peso Molecular , Receptores de Interleucina-2/biosíntesis , Linfocitos T/fisiología , Tunicamicina/farmacologíaRESUMEN
Studies from our laboratory have shown that anti-T12, a mAb which recognizes CD6, is a macrophage-dependent mitogen for human T cells and can augment T cell autoreactivity in vitro. To obtain additional information regarding the potential biological role of CD6 we sought to further characterize its biochemical properties. The CD6 molecule on 125I-surface-labeled T cells and by Western blot analysis was a monomer of mol. wt 130,000 under reducing conditions and mol. wt 117,000 under non-reducing conditions, suggesting the presence of intrachain disulfide bonds. The polypeptide contains a protease sensitive site. In activated T cells, the protein was serine phosphorylated. Analysis of biosynthetically labeled CD6 in the presence of tunicamycin revealed a reduction in mol. wt from 130,000 to 100,000, indicating that the polypeptide is extensively N-glycosylated. The mAb, anti-2H1, had been shown to activate T cells in combination with PMA or the anti-T11(3) mAb but, unlike anti-T12, not in the presence of macrophages alone. The present studies demonstrate by sequential immunoprecipitation that these two mAbs recognize the same polypeptide. However, Western blot analysis and indirect immunofluorescence cross-blocking studies demonstrate that the two mAbs recognize different determinants on CD6. Anti-T12 recognizes an epitope that is present only under non-reducing/non-denaturing conditions, while anti-2H1 recognizes an epitope that is also preserved under reducing/denaturing conditions. A direct comparison of activation properties of the mAbs confirmed that anti-T12 was optimally mitogenic in the presence of macrophages but not PMA, while, conversely, anti-2H1 was optimally mitogenic in combination with PMA but not macrophages, suggesting that the differences in epitope specificity may account for the distinct activation properties of each mAb. Taken together, the structural and functional data strongly suggest that the CD6 membrane glycoprotein may function as a physiologically important receptor structure on human T lymphocytes.
Asunto(s)
Antígenos CD/inmunología , Epítopos/inmunología , Activación de Linfocitos/inmunología , Linfocitos T/inmunología , Anticuerpos Monoclonales , Western Blotting , Fenómenos Químicos , Química , Electroforesis en Gel de Poliacrilamida , Humanos , Peso Molecular , Pruebas de PrecipitinaRESUMEN
Anti-T12 is a murine IgM mAb that recognizes the 130-kDa CD6 glycoprotein on mature human T lymphocytes. Examination of the in vitro effects of this mAb on freshly isolated T cells demonstrates that anti-T12 can induce T cell activation. Such activation is macrophage-dependent, and optimal stimulation occurs with 0.2 to 5 micrograms/ml of purified mAb. This response to soluble mAb is detectable at day 4 to 5 of culture, and peak [3H]TdR uptake is observed at day 7. In a highly similar fashion, the mAb causes a marked augmentation of the autologous mixed lymphocyte reaction, without altering the kinetics of that response. Although optimal anti-CD3 mAb induced mitogenesis is unaffected by anti-T12, suboptimal stimulation of macrophage-depleted T cells by small amounts of immobilized anti-CD3 can be dramatically enhanced when anti-CD3 and anti-T12 are cross-linked together. A soluble nonmitogenic anti-CD3 mAb completely inhibits anti-T12-mediated T cell activation. IL-2R expression is induced by anti-T12 stimulation in 10 to 30% of T cells, and T cell proliferation is substantially inhibited by anti-IL-2R mAb, indicating that anti-T12 induced T cell activation and proliferation utilizes an IL-2-dependent pathway. Isolated CD4+ but not CD8+ cells are stimulated to proliferate, but the CD8+ cells in unseparated T cell preparations activated by anti-T12 do proliferate comparably to the CD4+ cells in such cultures. These data indicate that relatively weak activation of T cells via the TCR/CD3 complex may be augmented significantly by CD6-mediated signals induced by the anti-T12 mAb. The findings suggest that the CD6 T cell membrane protein may have the capacity to function as a physiologically important structure involved in the regulation of T cell activation.
Asunto(s)
Anticuerpos Monoclonales/fisiología , Antígenos de Diferenciación de Linfocitos T/inmunología , Activación de Linfocitos , Linfocitos T/inmunología , Adyuvantes Inmunológicos/fisiología , Adulto , Adhesión Celular , Células Cultivadas , Humanos , Interleucina-2/fisiología , Persona de Mediana Edad , Monocitos/inmunología , Fenotipo , Receptores de Antígenos de Linfocitos T/fisiología , Linfocitos T/fisiologíaRESUMEN
The monoclonal antibodies anti-2H4 and anti-4B4 identify the suppressor-inducer (CD4+2H4+) and helper-inducer (CD4+4B4+) subpopulations of CD4 (T4+) lymphocytes, respectively. The cell surface phenotype of peripheral blood lymphocytes and synovial fluid lymphocytes in patients with rheumatoid arthritis and other inflammatory joint diseases was analyzed by use of these and other well-characterized anti-T-cell monoclonal antibodies. In the synovial fluid of patients with rheumatoid arthritis, there was a markedly decreased percentage of T4+2H4+ suppressor-inducer cells (3.1 +/- 1 percent) and an increased percentage of T4+4B4+ helper-inducer cells (29.1 +/- 9 percent) as compared with the proportions found in the peripheral blood of normal individuals (T4+2H4+: 19.0 +/- 6 percent, T4+4B4+: 23.0 +/- 7 percent). Moreover, patients with other chronic and acute inflammatory joint diseases exhibited highly similar synovial T-cell findings to those of the patients with rheumatoid arthritis (T4+2H4+: 4.2 +/- 3 percent, T4+4B4+: 33.1 +/- 9 percent). In contrast, there were no significant differences between the normal control subjects and patients with rheumatoid arthritis in the percentage of T4+2H4+ cells in peripheral blood lymphocytes, nor were there significant differences between normal control subjects, patients with rheumatoid arthritis, and patients with other joint diseases (osteoarthritis, gout, B27+ spondyloarthropathy, and psoriatic arthritis) in the number of T4+4B4+ cells or in the T4/T8 ratio of peripheral blood lymphocytes. However, very low numbers of T4+2H4+ (suppressor-inducer) peripheral blood lymphocytes were seen in a subgroup of patients, including five of seven with Reiter's syndrome and several patients with systemic rheumatic disease syndromes. In addition, although the percentage of T4+2H4+ cells in peripheral blood lymphocytes of patients with osteoarthritis (13.7 +/- 7 percent) and gout (14.3 +/- 7 percent) was decreased compared with that of normal controls (19.0 +/- 6 percent) (osteoarthritis versus normal controls p less than 0.025), this difference appeared to reflect alterations due to age rather than disease. Consistent with the phenotypic changes observed, synovial T cells were also functionally defective, since autologous mixed lymphocyte reaction-activated T4 cells from the synovial fluid of patients with rheumatoid arthritis failed to exhibit suppressor-inducer activity.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Anticuerpos Monoclonales , Artritis Reumatoide/inmunología , Artritis/inmunología , Linfocitos T Colaboradores-Inductores/clasificación , Linfocitos T Reguladores/clasificación , Artritis/sangre , Artritis Reumatoide/sangre , Femenino , Humanos , Prueba de Cultivo Mixto de Linfocitos , Masculino , Persona de Mediana Edad , Líquido Sinovial/citología , Linfocitos T/clasificaciónAsunto(s)
Linfocitos T/inmunología , Enfermedades Autoinmunes/inmunología , Diferenciación Celular , Membrana Celular/inmunología , Antígenos HLA/inmunología , Humanos , Síndromes de Inmunodeficiencia/inmunología , Inmunoterapia , Infecciones/inmunología , Activación de Linfocitos , Trastornos Linfoproliferativos/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/clasificación , Linfocitos T/fisiologíaRESUMEN
Although the importance of T cell lineage-specific surface glycoproteins and MHC gene products in soluble-, viral-, and alloantigen-stimulated immune responses has been well characterized, those involved in autoreactivity are less defined. To address this issue, we examined the ability of monoclonal antibodies to influence the autologous mixed lymphocyte reaction (AMLR). Here we show that both monoclonal anti-T3 and several monoclonal anti-T4 antibodies profoundly inhibited the autoreactivity of unseparated T cells, isolated T4+ cells, and isolated T8+ cells (cultured in the presence of irradiated T4 cells). Furthermore, monoclonal anti-T8 antibodies markedly inhibited the reactivity of the T8 cells co-cultured with irradiated T4 cells, only partially inhibited the proliferative response of unseparated T cells, and had no effect on the T4 cell AMLR responsiveness. Monoclonal antibodies against class II MHC (Ia) antigenic determinants blocked the AMLR between non-T cells and any of the above responder populations; in contrast, monoclonal anti-class I (HLA-A, B, C) antibodies inhibited the response of T8+ cells but not of isolated T4+ cells. These data support the notion that T4 and T8 antigens serve, respectively, as associative recognition elements for class II and class I MHC antigens during the AMLR, and further suggest that interactions involving non-T cell determinants and the T3-Ti- T cell antigen receptor complex are important in autologous reactivity.
Asunto(s)
Activación de Linfocitos , Prueba de Cultivo Mixto de Linfocitos , Receptores de Antígenos de Linfocitos T/fisiología , Linfocitos T/inmunología , Adulto , Anticuerpos Monoclonales/fisiología , Especificidad de Anticuerpos , Unión Competitiva , Separación Celular , Relación Dosis-Respuesta Inmunológica , Humanos , Cinética , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/clasificación , Linfocitos T/metabolismoRESUMEN
Previous studies using conventional hetero- or isoantisera have indicated the involvement of class II (Ia) molecules in presentation of soluble antigen by monocytes to inducer T lymphocytes, stimulation of inducer T cells in MLR, and recognition of Ia-bearing target cells by cytotoxic T lymphocytes (CTL). The experience in using monoclonal anti-Ia reagents capable of blocking these phenomena in the human system is limited. Recently, however, we have characterized a lytic IgG2a monoclonal antibody, 9-49, that binds to functionally significant class II molecules. This antibody blocks (in the absence of complement): (1) specific binding of peripheral blood lymphocytes (PBL) to antigen-pulsed monocyte monolayers, (2) proliferation of PBL in response to soluble antigen (tetanus toxoid or mumps) or cell surface class II antigen stimulation in allogeneic or autologous MLR, (3) proliferation of cloned T4+ (inducer) lymphocyte cell lines to class II antigens, (4) generation of cytotoxic lymphocytes during allogeneic MLR, and (5) recognition (and killing) of class II-bearing target cells by T4+ CTL clones. Proliferation and CTL activity of a T8+ clone is unaffected by the 9-49 antibody. These results indicate the usefulness of this monoclonal reagent in studies evaluating the functional role of Ia molecules in immune recognition phenomena.